The expression of apoptosisrelated proteins was examined by western blot analysis, to help examine the molecular mechanism causing statins caused apoptosis. As shown in Figure 6a, the expression of cleaved caspase 3 was remarkably enhanced in both EL4 and A20 cells following therapy with atorvastatin, fluvastatin Imatinib 152459-95-5 or simvastatin at 5 mM for 12 h, respectively. Furthermore, fluvastatin significantly increased the term of cleaved caspase 3 in both two cancer cells in a time-dependent fashion. We also addressed A20 cells with fluvastatin at concentrations ranging from 0?10 mM for 12 h. The words of cleaved caspase 3 and cleaved PARP, the well-known features of apoptosis, were significantly improved in a dose-dependent manner. The apoptosis problems are mainly determined Retroperitoneal lymph node dissection with a balance among pro and anti apoptotic members of the Bcl 2 family, frequently related to resistance of cancer cells to chemotherapy6. The expression of Bax, a professional apoptotic protein, was enhanced while expression of Bcl2, an anti-apoptotic protein, was decreased in fluvastatin addressed cells. Moreover, the activity of caspase 3 in A20 cells was also observed to improve in a dose-dependent fashion after-treatment with fluvastatin. Moreover, Akt pathway could be the major anti apoptotic molecular that confer resistance and the survival advantage of cancer cells against various chemotherapeutic agents. 25 We first examined whether fluvastatin down-regulated constitutive Akt activation in lymphoma cells. As demonstrated in Figure 6e, constitutive phosphorylation of Akt was suppressed by fluvastatin in a time dependent manner. We also analyzed the activation of MAPK cascades including p38 and Erk in cells. We discovered that fluvastatin markedly increased phosphorylation of p38 MAPK and decreased the phosphorylation of Erk pathway in a time-dependent fashion, respectively. These results indicate that fluvastatin could control the activation of PF299804 structure Akt and Erk pathways, but increase the activation of p38 MAPK pathway in lymphoma cells. Oxidative stress was involved in fluvastatin induced cytotoxicity. We examined the oxidative stress marker, intracellular ROS amounts, in lymphoma cells following treatment with fluvastatin at concentrations ranging from 20 mM for 6 h, to analyze the contribution of oxidative stress in fluvastatin cytotoxicity. As shown in Figure 7, treatment of lymphoma cells with fluvastatin notably increased intracellular ROS generation in a dose dependent manner, indicating the possible involvement of oxidative stress within the cytotoxic action of fluvastatin. To further investigate the signaling mechanism of ROS in fluvastatin caused cytotoxicity towards lymphoma cells, we incubated A20 cells with fluvastatin in the presence or absence of the thiol antioxidant N acetylcysteine.